Chemical Pathology 3 - Acid Base handling Flashcards
What are the 3 main buffering systems in the body?
bicarbonate is the main one
How is pH control achieved in the proximal convuluted tubule?
- H+ and HCO3- combine in tubule lumen to form H2CO3
- Carbonic anhydrase on tubule tumen membrane converts H2CO3 to H2O and CO2 and absorbs it into the tubule wall cell
- H2O + CO2 –> H2CO3 again inside the cell, via carbonic anhydrase II
- Bicarbonate is exchanged with chloride ions, releasing into the capillary
- H+ ions can be actively secreted into the tubule lumen, or transported via a sodium-proton exchanger
Recall 3 broad mechanisms of aetiology of metabolic acidosis
- H+ prodution (eg DKA)
- Decreased H+ excretion (eg renal tubular acidosis)
- Bicarbonate loss (eg intestinal fistula)
Describe the change in the acid-base equilibrium in a metabolic acidosis
Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2
Extra H+ produced by acidosis pushes reaction RIGHT
CO2 production increases –> blown out by increased ventilation
Describe the change in the acid-base equilibrium in a respiratory acidosis
a) acutely
b) chronically
Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2
a) acutely:
Excess CO2 produced by reduced ventilation pushes reaction LEFT, so more H+ and HCO3- is produced (this is PRIOR TO COMPENSATION)
b) Chronically:
CO2 remains raised (due to reduced ventilation), and HCO3- remains raised to maintain physiological pH - so in chronic COPD etc you would see elevated bicarbonate
Describe the change in the acid-base equilibrium in a metabolic alkalosis
Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2
Pathology = decreased H+ / increased HCO3-
- loss of H+ (pyloric stenosis)
- increased ingestion of bicarbonate (antacids)
- hypokalaemia (hypkalaemia and alkalosis go together)
Either way - need to regenerate H+
Therefore, EQUILIBRIUM moves LEFT
To do this: resp rate decreases (to increase CO2)
What are the possible causes of metabolic alkalosis?
H+ loss: pyloric stenosis, hypokalaemia
HCO3- excess: lots of Rennies
Describe the acute change in the acid-base equilibrium in a respiratory alkalosis
Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2
Hyperventilation –> reduced CO2
Reaction moves RIGHT to restore CO2
Describe the chronic change in the acid-base equilibrium in a respiratory alkalosis
Equilibrium =
HCO3- + H+ H2CO3 H2O + CO2
Acutely, reaction moves RIGHT to restore CO2 (so you get low H+ and HCO3-)
Chronically, kidneys compensate by reducing H+ excretion - so H+ returns to normal, but HCO3- and CO2 remain low
When can you get a mixed respiratory and metabolic acidosis?
eg COPD patient with diabetes mellitus
COPD- respiratory acidosis
Diabetes mellitus- metabolic acidosis
Normal pH
7.35 – 7.45
Normal CO2
4.7 – 6kPa
Normal bicarb
22 – 30 mmol/l
Normal O2
10 – 13kPa
Biochemical abnormlaities and causes of metabolic acidosis
pH: low
pCO2: low
Hco3: low
Causes
1) High AG: KULT
Ketones
Uraemia
Lactic acid
Toxins- ethylene glycol, metformin (biguanide), methanol, paraaldehyde, salicylate
2) Normal anion gap
Diarrhoea (small bowel GI loss of HCO3), Acetazolamide (CA inhibitor), high output stoma, pancreatic fistula (loss of bicarb), Addison’s, renal tubular acidosis, ammonium chloride ingestion
Metabolic alkalosis
pH: high
CO2: high (due to the hypoventilation)
Bicarb: high
causes
Vomiting (H+ loss)(bulimia), Loop diuretics (K+ depletion), hypokalaemia, Conn’s (hyperaldosteronism, (immediate)
K+ loss), antacid use, burns
Respiratory acidosis
pH: low
CO2: high
bicarb: high
causes
Hypoventilation (T2 resp failure): Acute/chronic lung disease (commonest = COPD), opioids, sedatives, neuromuscular weakness
Normal/high PaCO2 worrying - ITU RV/vent support (exhaustion)
Respiratory alkalosis
pH: high
co2: low
bicarb: low
Causes:
Hyperventilation: Stroke; SAH, meningitis, asthma, alkalosis
anxiety, PE, pregnancy, altitude (hypoxaemia),
↓renal [HCO3-]
salicylates (early – brainstem stimulation)
Calculation of anion gap
(Na+ + K+) – (Cl- + HCO3)
Osmolality (measured) – Osmolarity (calculated)
Normal osmolar gap = < 10 • An elevated osmolar gap provides indirect evidence for the presence of an abnormal solute • The osmolar gap is increased by extra solutes in the plasma (e.g. alcohols, mannitol, ketones,
lactate) • Can be raised in advanced CKD due to retained small solutes • Helpful in differentiating the cause of an elevated anion gap metabolic acidosis
What is the key equation that explains buffering?
H+ excreted by kidneys
CO2 excreted by lungs
What abnormality of acid base do you get in aspirin overdose?
Mixed respiratory alkalosis and metabolic acidosis
Why?
a) Aspirin stimulates respiratory centre–>respiratory alkalosis
b) Aspirin inhibits bicarbonate reabsorption in kidney –>metabolic alkalosis
Mnemonic for remembering causes of raised anion gap
MUDPILES
Metformin/methanol
Uraemia
DKA
Paraldehyde
Iron
Lactate
EThanol
Salicylcates
